Like this:

As a commentator, it’s difficult to know where to begin some days, commenting on what’s going on around me.

***

I can always fall back on weird and wonderful things I see, or experiences I’m having and what they mean to me.

***

I really don’t want this to be a personal journal. For one thing, who cares? I mean, those who care are already in my life and know all this stuff. Besides, I don’t want to blab all over the Internet about most of what’s happening with me because it’s personal.

***

What the world looks like from my point of view. Totally personal and independent, never having been a card-carrying member of any movement, party, or union. Largely disdainful of all organizations (it seems like they too often become self-perpetuating monstrosities run by power-mad dictators), yet aware that we are all interdependent, I seek to find what my principles are.

***

I have a conversation partner and fellow intellectual, but I can see how being in a milieu of pundits and politicians would sharpen one’s wit even more. Or would it make you pull your punches, since you’d lose lunches?

Care to share? Here are some ways:

Not physically “where am I?” I reside in the USA and blog from my basement office in a condominium. No, where am I in my quest for meaning? My metanovel? My expermintal nonfiction work?

Why I’m right here, keying this in, watching the letters appear, forming words and phrases and sentences and paragraphs to what end, we shall find out. Unlike a play or movie or novel, a work of experimental nonfiction does not have to know how it’s going to end — I mean whoever is creating the X-non-fic doesn’t have to know how it’s going to end; it may never end; it may have a different end point each time it is experienced; it may render the concepts of “beginning” and “end” meaningless.

“I’ll turn any offer down,” the March Hare might have said at the tea party, “because anything with a beginning must surely come to an end. So why begin?”

“I hate endings, too,” the Mole might muse, while another furry creature becomes rapt with the idea of beginning at the end.

“Don’t start a fight you can’t finish,” is another variation, and then there’s Paul’s First Law of Literature: Never start a novel unless you know how it will end. This fits well with the first corollary: Begin your novel as close to the end as possible.

Like this:

[So this is the type of cool, techie online article I write. It ran on BrassRing.com October 14, 2000]

A lean, mean, gene sequencing machine

By Paul Zukowski

The news about the mapping of the entire human genome was all over the media this summer [CE 2000]. It was hailed as a scientific breakthrough as important as splitting the atom or landing on the moon.

While the government-funded Human Genome Project had labored for 10 years using multiple institutions working on pieces of the project, a California company named Celera Genomics took less than two years to race through the entire 100,000 gene jungle and create a complete map of the 3.2 billion base pairs.

How was this technological triumph accomplished? What sort of machines were involved? And what are they going to do next?

The computerized machines behind the gene-mapping achievement are called gene sequencers in general and the ABI Prism 3700 DNA Analyzer in particular. These $300,000 wonders of modern technology were employed in large numbers to do the infinitely detailed work of analyzing the exact structure of human genes. An impressive array of 300 of the machines was used at Celera Genomics and a lesser number by the Human Genome Project. In total over 1,000 ABI Prism 3700s are at work in labs worldwide.

The machines are made by Applied Biosystems Inc., a sister company of Celera Genomics within PE Corporation, located just south of San Francisco in Foster City, Calif. (Applied Biosystems had been conducting business as PE Biosystems for several years before recently returning to its original name.)

An ABI Prism 3700 is about the size and shape of a medium-sized refrigerator. Each machine houses 96 capillary tubes that separate the DNA sequences by size and allow special fluorescent markers to be read by laser. This data is then converted to digital form for analysis. The process is so highly automated that one technician can tend 15 machines, inserting samples and removing completed work.

This is in stark contrast to the messy, cumbersome gel-between-glass-plates method of gene sequencing still in use on some labs. Most of us have seen these fuzzy x-ray-like films of rows of little black smudges.

Applied Biosystems developed a method of gene fractionation using a single capillary in 1987, and by 1998 had ramped this up to an industrial level with the ABI Prism 3700. That’s when Craig Venter, who was at The Institute for Genomic Research (TIGR) at the time, saw this system in development and he knew it would allow him to sequence the human genome and do it much faster than existing technology permitted. PE Corporation and Dr. Venter jointly formed Celera Genomics in 1998 with Venter as president. [It was later revealed that the human genome being sequenced was contributed by Venter.]

The first step in doing any sort of DNA analysis is making enough copies of your microscopic sample to work with. That takes a process called PCR — polymerase chain reaction. That methodology was developed by Cary Mullins, a scientist in the Bay Area at Cetus Corporation.

Once you have your sequences in sufficient numbers, markers are attached to the beginnings and ends so they can be identified. Then comes the electrophoresis.

“The DNA sample is drawn into a capillary about the width of a human hair by a pump system,” explained Applied Biosystems spokesperson Jay Rhodes. An electric current causes the DNA to separate according to molecular weight, “and then the capillary runs the separated DNA in front of the laser.” That provides a reading of the markers.

This is going on in 96 capillaries in each of the 300 machines, 24-hours a day.

What are the ABI Prism 3700s analyzing now that the human genome is mapped? Would you believe a mouse?

“Celera has completed 95% of the mouse genome,” said Rhodes. “And everyone agrees that having other genomes to compare the human genome to will be very valuable. The fruit fly genome was done before the human genome, for instance.” Both animals are used extensively in laboratory testing. Lab rat genes will be next.

“It’s all about offering researchers who were looking at cancer, diabetes, hypertension, and those kinds of things a greater ability to sift through the forest [of genes] and find the tree or trees that are associated with disease and treat them,” said Rhodes.

Another use of Applied Biosystems’ technology is in studying variations in the genes of each individual person. These variations not only determine hair color, but also tell scientists how a person will react to a drug or what diseases they are prone to. They are called single nucleotide polymorphisms, or SNPs — pronounced “snips.”

Researchers have already discovered 300,000 SNPs and are on their way to a million by 2001. Companies like Millennium Pharmaceuticals, Nanogen, and Orchid Biocomputer, along with the publicly funded SNP Consortium are working to catalog SNPs.

And beyond SNPs, Rhodes said the next frontier for analysis using Applied Biosystems’ machines are those substances the genes help create — proteins. All this is plenty to keep the 4,000 worldwide employees of Applied Biosystems and the 600 at Celera busy far into the future.